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Pharmaceutical preparations are drugs manufactured in accordance with specific dosage form requirements for use by patients, with the aim of meeting the needs of treating or preventing diseases. Inhalation formulations are liquid or solid preparations in which the active drug is dissolved or dispersed in a suitable medium, and are administered to the lungs in the form of vapor or aerosol to exert local or systemic effects; they represent the preferred method of administration for treating respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Common inhalation formulations include inhalation aerosols, nebulized liquid formulations, and inhalation powder aerosols. This article first introduces the formulation development of inhalation aerosol drugs. An inhalation aerosol is a preparation in which a drug, along with a propellant and other components, is enclosed in a pressure-resistant container equipped with a metering valve system; during use, the pressure of the propellant is utilized to release the contents in mist form for inhalation into the lungs. The basic components of an aerosol formulation include the drug and a propellant. In addition to the propellant, solubilizers, surfactants, stabilizers, and the like may also be added. 1. What are the common ingredients in aerosol formulations? Propellants are substances that provide the propulsion for aerosols, and they generally also serve as solvents or diluents for the drugs. The prescription components of aerosols can generally be divided into: (1) the prescription contains only the active ingredient and a propellant, with the active ingredient dissolved or suspended in the propellant ； (2) The prescription contains drugs, propellants, and solubilizers; solubilizers such as anhydrous ethanol, etc ； (3) The formula contains drugs, propellants, solubilizers, and surfactants. Adding surfactants to the formula generally helps the drugs disperse more evenly in the solvent, and it also lubricates the components to improve the performance of the valve system ； (4) In addition to the components mentioned above, other ingredients may also be added, such as antioxidants to enhance drug stability and pH regulators. Due to differences in the physicochemical properties and stability of drugs, aerosols are generally developed in two forms: solution type and suspension type. For the two different types of aerosols, particular attention must be paid to the properties of the respective active pharmaceutical ingredients, which should be thoroughly understood and studied prior to formulating the prescription as well as during the prescription development process. Drug formulation development can, based on pre-prescription information and by utilizing formulation techniques that enhance bioavailability, create drug formulations that meet the requirements of the formulation stage in innovative drug development. Medici can provide clients with services prior to drug formulation as well as research related to drug formulation, offering reliable data for CMC submission documents. For solution-type aerosols, it is necessary to investigate their solubility, chemical stability, and impurity profile ； For suspension-type aerosols, it is necessary to study the crystal form and polymorphism of the raw materials, the particle size distribution of the raw materials, the density of the drug, the morphology of the powder particles, surface energy, moisture content, and hygroscopicity. Compared to solution-type aerosols, suspension-type aerosols generally require the evaluation and study of more properties of the active pharmaceutical ingredients, and are usually more challenging to develop. 2. Challenges in aerosol development: The difficulty in developing aerosols lies in the many factors that affect the quality of these products, especially in the case of suspension-type aerosols. In addition to formulation factors such as the properties of raw materials and excipients, as well as the composition and dosage of the formula, the tank itself, particularly the valves and actuators, also has a significant impact. Furthermore, domestic production processes and equipment are relatively backward; for some suitable ingredient formulations, it is difficult to implement them using such processes or equipment, making industrialization challenging. When developing a prescription, the formula for the contents can be designed based on the specifications of the valve system, the specifications of the drug, and the total number of doses, including the amount of active ingredient to be used ； Alternatively, the specifications of the valve system can be selected based on the desired concentration of the active ingredient in the prescription and the formulation details; thereafter, the prescription and the amount of the main active ingredient used can be adjusted appropriately according to the experimental results, ensuring that all specifications meet the required standards first. The development of the aerosol formula and the selection of containers, valves, and actuators can be carried out simultaneously. The formulation components of the solution can be adjusted as needed; for example, anhydrous ethanol may be added to meet process feasibility requirements or to ensure the dissolution of the drug ； Surfactants were added to meet the requirements for drug dispersibility ； Antioxidants, pH regulators, and the like are added to meet the stability requirements of the drug. When developing a prescription, it is first necessary to understand the general requirements for prescription factors in inhalation aerosols, such as the particle size requirements for suspension-type aerosols and the influence of moisture content in the contents. Secondly, it is necessary to understand and evaluate various formulation factors (such as the properties of active and inactive ingredients, formulation composition, and dosage) as well as the quality attributes of inhalation aerosols (such as the appearance of the drug solution, content per dose, consistency of the delivered dose, total number of actuations, particle size distribution of the mist droplets, and the aerodynamic distribution of the droplets/particles – using methods such as two-stage impact collection and ACI/NGI multi-stage impact collection), as well as impurities, leakage rate, and spraying pattern. By analyzing which formulation factors may affect which quality attributes of the aerosol, it is possible to carry out more targeted formulation development. For example, the flocculation and sedimentation of drugs in suspension-type aerosols, as well as their redispersibility, can be affected by properties of the raw materials such as particle size distribution, surface energy, density, and particle shape, as well as by the composition and dosage of the formula. The impact of the type and proportion of propellants in the prescription ； The effect of the ratio and amount of ethanol to propellant (such as the addition of ethanol) ； Effects of the type and amount of wetting agent (such as the addition of a wetting agent) ； The impact of moisture content, and so on. Therefore, during formulation development, it is necessary to thoroughly study the impact of the aforementioned formulation factors on the physical stability of suspension-type aerosols, identify the key formulation factors, and exercise appropriate control over them. Of course, the aforementioned formulation factors may have a direct impact on other quality attributes of inhaled aerosols. For example, different vapor pressures of propellants, various proportions of propellants, as well as different ratios of ethanol to propellants, all have a direct effect on the particle size distribution and the aerodynamic distribution of the mist droplets; they may also have a significant impact on other quality attributes ； The amounts of ethanol and propellant affect the concentration of the solution, thereby influencing the content per inch ； Stabilizers have a direct impact on related substances, and so on; therefore, formula development is a process that involves the simultaneous evaluation of multiple factors and various quality attributes of the formulation. It requires systematic consideration and research, and when necessary, DOE can be used to study the formulation. There are numerous factors that influence the quality attributes of inhaled aerosols, making their development somewhat challenging. In addition to the formulation factors mentioned above, the container, valves, and actuators can have a significant impact on various quality attributes such as the particle size distribution of the droplets in the aerosol, the aerodynamic distribution of those droplets, impurities (including extracts), leakage, consistency, and the visual appearance of the drug solution. Therefore, these aspects should be studied simultaneously during formulation development.